Several agents were found to enhance macrophage and natural killer cell tumoricidal activity (poly ICLC, lentinan, thymopoeitin fractions, MVE, glucan and human chorionic gonadotropin). The enhanced activity was neutralized by interferon antibody, indicating that interferon is the direct activating factor. The tumoricidal activity of interferon may be due to its capacity to enhance macrophage and natural killer cell reactivity to tumor antigens. Prostaglandins E1 and E2 negate macrophage tumoricidal activity via "shut off" mechanism. TPA, a potent inflammatory and tumor-promoting agent possesses two opposing influences on macrophage reactivity. Conditioned medium from macrophages pulsed with TPA enhanced M109 carcinoma colony formation in vitro. Splenocytes incubated with TPA produced macrophage activating factor. Human chorionic gonadotropin enhanced macrophage and natural killer activity. Human monocyte cultures exposed to human interferon exerted a stronger cytotoxic effect on the Raji lymphoma tumor cell line. Significant adjuvant effect was attained with MVE when it was combined with B16 melanoma vaccine. Increased survival was attained in L1210 leukemia when Azimexon (BM 12.531) and MVE were combined with chemotherapy.